rs199662534
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001164508.2(NEB):c.4904C>T(p.Thr1635Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001164508.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEB | NM_001164507.2 | c.4904C>T | p.Thr1635Ile | missense_variant | 41/182 | ENST00000427231.7 | NP_001157979.2 | |
NEB | NM_001164508.2 | c.4904C>T | p.Thr1635Ile | missense_variant | 41/182 | ENST00000397345.8 | NP_001157980.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEB | ENST00000397345.8 | c.4904C>T | p.Thr1635Ile | missense_variant | 41/182 | 5 | NM_001164508.2 | ENSP00000380505 | P5 | |
NEB | ENST00000427231.7 | c.4904C>T | p.Thr1635Ile | missense_variant | 41/182 | 5 | NM_001164507.2 | ENSP00000416578 | A2 | |
NEB | ENST00000409198.5 | c.4904C>T | p.Thr1635Ile | missense_variant | 41/150 | 5 | ENSP00000386259 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249210Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135186
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461670Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727122
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74354
ClinVar
Submissions by phenotype
Nemaline myopathy 2 Uncertain:2Benign:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 29, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 20, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 09, 2024 | The c.4904C>T (p.T1635I) alteration is located in exon 41 (coding exon 39) of the NEB gene. This alteration results from a C to T substitution at nucleotide position 4904, causing the threonine (T) at amino acid position 1635 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 11, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at